1. Field of the Invention
This invention relates to the general field of animal therapy. More particularly, this invention is directed to bone disorder therapy in animals, including man. The present invention relates to treatment, prevention, or delay in onset of calcium related bone disorders such as osteoporosis in humans, osteochondrosis in swine and other mammals and poultry, and dyschondroplasia in poultry This invention also pertains to other related bone diseases known in the medical and veterinary sciences, particularly to those related to osteoid calcification disorders.
2. Description of Related Art
Over the years a wide variety of experiments have been conducted throughout the world utilizing zeolites of many different types in the feeding of animals for varying reasons. Most of these experiments have been in the fields of animal nutrition or animal husbandry, e.g. in increasing the production of food animals or their food products Animals fed zeolites were poultry, cattle, sheep and swine Zeolites fed to the animals were mainly naturally occurring zeolites, i.e. or those zeolites found in nature. Although some degree of success in some areas was achieved, most of the results were unfavorable.
An article by C. Y. Chung et al from Nongsa Sihom Youngu Pogo 1978, 20 (Livestock) pp. 77-83 discusses the effects of cation exchange capacity and particle size of zeolites on the growth, feed efficiency and feed materials utilizability of broilers or broiling size chickens. Supplementing the feed of the broilers with naturally occurring zeolites, such as clinoptilolite, some increase in body weight gain was determined. Chung et al also reported that earlier results at the Livestock Experiment Station (1974, 1975, 1976--Suweon, Korea) Showed that no significant difference was observed when 1.5, 3, and 4.5 percent zeolite was added to chicken layer diets.
U.S. Pat. No. 3,836,676 issued to Chukei Komakine in 1974 discloses the use of zeolites as an adsorbent for adhesion moisture of ferrous sulfate crystals in an odorless chicken feed comprising such crystals and chicken droppings.
Experiments were conducted in Japan on the use of natural zeolite minerals as dietary supplements for poultry, swine and cattle. Significant increases in body weight per unit of feed consumed and in the general health of the animals was reported; (Minato, Hideo, Koatsugasu 5:536, 1968). Reductions in malodor were also noted.
Using clinoptilolite and mordenite from northern Japan, Onagi, T. (Rept. Yamagata Stock Raising Inst. 7, 1966) found that Leghorn chickens required less food and water and gained as much weight in a two-week trial as birds receiving a control diet. No adverse effects on health or mortality were noted. The foregoing Japanese experiments were reported by F. A. Mumpton and P. H. Fishman in the Journal of Animal Science, Vol. 45, No. 5 (1977), pp. 1188-1203.
Canada 939,186, issued to White et al in 1974 (U.S. Pat. No. 4,393,082, issued Jul. 12, 1983) discloses the use of zeolites having exchangeable cations as a feed component in the feeding of urea or biuret non-protein nitrogen (NPN) compounds to ruminants, such as cattle, sheep and goats. Natural and synthetic as well as crystalline and non-crystalline zeolites are disclosed. Zeolites tested using in vitro techniques included natural zeolites, chabazite and clinoptilolite and synthetic zeolites X, Y, F, J, M, Z, and A. Zeolite F was by far the most outstanding and zeolite A was substantially ineffective.
An article by W. L. Willis et al entitled Evaluation of Zeolites Fed to Male Broiler Chickens published in Poultry Science, 61, 438-442 (March, 1982) discloses the feeding of natural zeolites such as clinoptilolite to male broiler chickens in amounts of 1, 2 and 3 weight percent.
In a study at the University of Georgia, both broilers and layers were fed small amounts (about 2%) of clinoptilolite, a naturally occurring zeolite from Tilden, Texas. The egg shells from the hens receiving zeolite were slightly more flexible as measured by deformation, slightly less strong as measured by Instron breaking strength, and had a slightly lower specific gravity. The differences in egg shell quality were very small. This type of zeolite was ineffective in producing a stronger egg shell. An article written by Larry Vest and John Shutze entitled The Influence of Feeding Zeolites to Poultry Under Field Conditions summarizing the studies, was presented at Zeo-Agriculture '82.
A study by H. S. Nakaue on feeding White Leghorn layers clinoptilolite, reported in Poultry Science 60, 944-949 (1981), disclosed no significant differences in egg shell strength between hens receiving the zeolite and hens not receiving the zeolite.
European Patent Application 0119992, published Sep. 26, 1984, discloses the feeding of the natural zeolite, chabazite, to poultry, namely turkeys In a test utilizing 480 tom turkeys, those turkeys fed 2 weight percent chabazite ore showed improved weight gain and feed efficiency over those turkeys fed similar amounts of sodium exchanged zeolite A and calcium exchanged zeolite A; however, the turkeys fed zeolites showed an increase in mortality rate over those turkeys in which no zeolites were fed. The turkeys fed sodium exchanged zeolite A showed significantly less weight gain and less feed efficiency than those turkeys fed no zeolites at all, and the turkeys fed calcium exchanged zeolite A showed about the same weight gain as the control, but had even less feed efficiency than the turkeys fed the sodium exchanged zeolite A.
Japan 59-203450, published Nov. 17, 1984, describes the use of synthetic metal aluminosilicates, preferably type A, type P, type X or type Y zeolites, as feed additives for livestock, pets, cultured fish, etc. with active ingredients consisting of basicity-adjusted aluminosilicates to an equilibrium pH of "10.5 or less"; preferably between 9.5 and 4.5. The feed additives are said to have a digestion-regulating effect, i.e., a high antacid effect in the pH range of 3 to 5. They also are said to appear to be superior as Co.sup.++ donors and donors of other minerals. In a single experiment of 100 piglets, using 2 weight percent calcium aluminosilicate, either amorphous or type A zeolite, no significant differences between the two forms were observed. Body weight for piglets fed the calcium zeolites showed an increase but feed utilization rate was down slightly.
U.S. Pat. No. 4,537,771 relates to the use of synthetic zeolites as antacids The report to the Great Lakes Science Advisory Board of the International Joint Commission on the Health Implications of Non-NTA Builders, October, 1980, Windsor, Ontario, Revised March, 1981, summarizes toxicity studies conducted on zeolite A using various animals. Gloxhuber et al also discuss the toxicology of zeolite A; Chemical Toxicology, 21:(2), pp. 209-220 (1983). Nolen et al, found no evidence of teratogenicity of zeolite A in rats; Food and Cosmetic Toxicology, 21:(5), 697 (1983). Cook et al, Environ Sci. Tech., 16, (No. 6) 344 (1982) discuss zeolite A hydrolysis and degradation. The uptake of acid was measured at pH values in the range of 3-9.
Benke et al discuss urinary silicon excretion of rats following oral administration of silicon compounds including sodium zeolite A; Food and Cosmetic Toxicology, 17, pp. 123-127 (1979).
The reference, Tentative Evaluation of the Health Aspects of Certain Silicates as Food ingredients (1977), prepared by the Bureau of Foods of the Food and Drug Administration, summarizes the scientific literature from 1920 to 1973 concerning the health aspects of certain silicates as food ingredients.
E. M. Carlisle, Nutrition Reviews, 40, (7), 193-198 (1982) discusses the nutritional essentiality of silicon. She also discusses silicon in bone formation in chapter Four of Silicon and Siliceous Structures in Biological Systems, Simpson, T. L., ed. B. E. Springer Verlag, New York (1981), pp. 69-94.
Berlyne et al, Nephron, 43, 5 (1986), discusses urinary silicon excretion. Charnot et al studied the endocrine interaction of silicon metabolism, Societe D'Endocronologie, 397-402 (1971), Biochemistry of Silicon and Related Products, Plenum Press, 269-280 (1978).
Merkley, J. W., The Effect of Sodium Fluoride and Sodium Silicate on Growth and Bone Strength of Broilers, Poultry Science 62, 798 (1983) discloses that a decrease in humeri strength was observed when one wing of broilers was immobilized for two weeks in the control and sodium fluoride treated groups. The loss of strength was not significant in the sodium silicate group.
Reagan, Luther M., Effects Of Adding Zeolites To The Diets Of Broiler Cockerels, Thesis Submitted to Colorado State University, Recommended for Acceptance Apr. 25, 1984, had among its primary objectives "analysis and identification of functional properties of zeolites as they relate to bone breaking strength". No differences were detected in the zeolite treated rations concerning bone strength or bone ash.
Other studies in connection with the aforementioned patent application of Laurent and Sanders indicate that zeolite A has a positive effect upon structural maintenance and strength of bone within six weeks of administration, and that zeolite A in poultry diets causes a reduced incidence and severity of tibial dyschondroplasia (osteochondrosis) and enhanced absorption of .sup.47 calcium; see also Edwards, Annual Meeting of the Poultry Science Assoc., North Carolina State University (1986). Research of Laurent et al has also resulted in the discoveries that zeolite A (i) decreases mortality in the rate of laying hens, U.S. Pat. No. 4,610,883; Roland et al, J. Poultry Sci., 64:1177 (1985), Miles et al, Nutrition Reports International (1986); (ii) increases quality of poultry eggshells, U.S. Pat. No. 4,556,564; (iii) and reduces heat stress, Influence of ETHACAL Feed Component On Production Parameters Of White Leghorn Hens During High Ambient Temperature, (paper presented at the Southern Poultry Science Annual Meeting, Atlanta, Ga., Jan. 27-28 (1987). It has also been discovered that zeolite A inhibits kidney stones or urinary calculi in lambs, Laurent and Pond, U.S. Pat. No. 4,515,780.